Abstract
The enantiomers of the N,N-dimethylamino (1), N,N-diethylamino (2), and N,N-dibutylamino (4) derivatives of 8-hydroxy-2-(dipropylamino)tetralin (8-OH DPAT; 3) have been synthesized. The compounds have been tested for activity at central 5-hydroxytryptamine and dopamine receptors by use of biochemical and behavioral tests in rats. In addition, the ability of the enantiomers of 1-4 to displace [3H]-8-OH DPAT from 5-HT1A binding sites was evaluated. Rank order of potencies in the in vivo tests corresponded to that observed in the 5-HT1A binding assay. In all three tests, the enantiomeric potency ratio was about 10 for 1 and 2 and only around 2-4 for 3 and 4. The more potent enantiomer of 1-3 had the R configuration. In contrast, (S)-4 seemed to be slightly more potent than (R)-4.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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5-Hydroxytryptophan / biosynthesis
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8-Hydroxy-2-(di-n-propylamino)tetralin
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Animals
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Brain Stem / drug effects
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Brain Stem / metabolism
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Chemical Phenomena
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Chemistry
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism
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Dihydroxyphenylalanine / biosynthesis
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Dopamine / biosynthesis
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Limbic System / drug effects
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Limbic System / metabolism
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Male
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Motor Activity / drug effects
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Naphthalenes / pharmacology*
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Rats
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Rats, Inbred Strains
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Receptors, Dopamine / drug effects*
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Receptors, Dopamine / physiology
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Receptors, Serotonin / drug effects*
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Receptors, Serotonin / physiology
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Serotonin / biosynthesis
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Stereoisomerism
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Structure-Activity Relationship
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Tetrahydronaphthalenes / chemical synthesis
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Tetrahydronaphthalenes / pharmacology*
Substances
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Naphthalenes
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Receptors, Dopamine
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Receptors, Serotonin
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Tetrahydronaphthalenes
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Serotonin
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Dihydroxyphenylalanine
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8-Hydroxy-2-(di-n-propylamino)tetralin
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5-Hydroxytryptophan
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Dopamine